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It’s Not What You Know, But What You Do With What You Know**
Ilaria Capua, D.V.M., Ph.D.
Director, Division of Comparative Biomedical Sciences,
Istituto Zooprofilattico Sperimentale delle Venezie, Padova, Italy
Summary
Two and a half years after the emergence of the first pandemic influenza virus of the 21st century, we
are certain there is space for improvement in the area of preparedness, and thus for mitigation. The
persistence of a dogmatic approach for controlling factors underlying the emergence of influenza virus
strains that are capable of both jumping the species barrier and spreading among human populations
has produced negative outcomes. Such consequences range from mistrust of public health
authorities to the delayed availability of vaccines. For this reason, our prediction skills must be
improved, and the first step in this direction is to be able to comprehensively analyze the pandemic
potential of animal influenza viruses. Paradoxically, we have the dataset, but we just do not look at it
with the appropriate tools and mindset. What we need is a “One Flu” approach. This approach
includes the development of a permanent observatory (either virtual or physical), including analytic
tools that can identify and grade animal strains that fulfill some or all the requisites of a pandemic
virus before the virus becomes a problem in humans. This would enable us to have a library of
“potentially pandemic” strains which can be used as seeds for vaccine manufacture to ensure product
availability in a shorter period of time. The creation of an interdisciplinary data library requires an
ongoing and timely mechanism to ensure transparency between the veterinary and medical
communities on genetic and epidemiological data, which are routinely collected through surveillance
efforts worldwide; such a library is in line with the “One Health” vision. This interdisciplinary approach
would pave the way for similar methodologies applicable to other emerging and zoonotic infectious
diseases, thus complementing other efforts in the fields of preparedness, response, and mitigation.
Current realities
More than two years after the emergence and spread of the first influenza pandemic of the new
millennium, we are aware of how our prediction skills need to improve on many fronts. The
emergence of the H1N1 virus strain responsible for the 2009 influenza pandemic (PDM 2009 H1N1)
was an unexpected event for most influenza scientists. The viral subtype and the geographical and
biological origin of the virus were distant from both the geographic regions and the areas of research
where significant funds for influenza were invested. The influenza epicenter was deemed to be
Southeast Asia, and the epizootic of a highly virulent H5N1, with a previously unseen capacity to jump
the species barrier, was believed to be the most likely candidate for the next human pandemic.
In reality, PDM 2009 H1N1 originated from Central America rather than Southeast Asia. Additionally,
PDM 2009 H1N1 was of a subtype not included in the pre-pandemic candidate list, was relatively mild
(compared to the virulence of H5N1), and emerged from swine rather than birds. In hindsight, the
pandemic potential of some animal viruses was underestimated. These examples illustrate the
importance of improving our prediction skills.
Until 2009, the real and perceived threat posed by H5N1 viruses had drawn significant resources to
issues related to avian influenza viruses, particularly in Eurasia. Influenza infections in mammalian
species were neglected, particularly in the Americas. In addition, a rather dogmatic approach
suggested that to ignite a pandemic, the virus had to be of a different subtype to those that were
circulating in the human population as seasonal strains. These two blind spots impeded the
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identification of the emerging risk in Central America.
Possibly the only correct prediction attempt was that a new pandemic virus would very rapidly infect
the entire world population, exploiting opportunities offered by globalization. Although PDM 2009
H1N1 is considered a relatively mild pandemic, it resulted in significant mortality data and years of life
lost. Had there been a suitable pre-pandemic vaccine available in time, morbidity and mortality could
have been greatly reduced.
In addition, “betting on the wrong virus” (i.e., H5N1) has caused a general sense of mistrust of
international health organizations and resulted in avoidable damages to the perception of international
health policies aimed at preparedness and mitigation.
Scientific opportunities and challenges
Looking to the future, it is important to bear in mind that we may be baffled again by this disease.
Although the recent pandemic was not as severe as had been envisaged for a pandemic caused by
H5N1, the future occurrence of a severe influenza pandemic cannot be ruled out. Avian viruses (e.g.,
H5N1) and others with zoonotic potential (e.g., H9N2) are still endemic in large portions of the eastern
hemisphere. Swine influenza viruses and other mammalian viruses are also circulating at a global
level, and together with viruses of wild and domestic poultry, represent a unique evolving gene pool
containing the precursors of the next human pandemic strain.
We have to recognize that vast improvements in capacity building have been achieved as a result of
the H5N1 global crisis. Investments in infrastructure and training have yielded a network of scientists
with improved influenza diagnostic capacity. Thousands of viral isolates with zoonotic potential have
been obtained through surveillance efforts. However, the genetic information has not been fully
exploited. An in-depth knowledge of these viruses would allow the scientific community to obtain a
better picture of the pandemic potential of selected strains, and enable the development of better
prevention and mitigation strategies.
Influenza infections still represent a major threat to mankind, to the livelihood of rural villages, and to
the health and productivity of animals. The recent pandemic highlights a need to improve our
prediction capacities to enact more efficient prevention strategies through integrated research and
surveillance efforts, embracing both animal health and public health. This is in line with, and possibly
the best example of, the One Health vision: a multidisciplinary collaborative approach to improve the
health of humans, animals, and the environment, endorsed by the Food & Agriculture Organization of
the United Nations (FAO), the World Organisation for Animal Health (OIE), and the World Health
Organization (WHO). The One Flu initiative would result in international synergies, bridging gaps
between medical and veterinary scientists, permanent monitoring of virus evolution and epidemiology,
and the best exploitation of investments in capacity building. Above all, it would be a challenge and
an opportunity to apply a One Health approach to influenza (i.e., One Flu). Moreover, this approach
could possibly act as a model for other emerging zoonotic diseases.
Policy issues
x
A permanent observatory, which contains existing genetic and epidemiological information on
strains that are collected globally through animal and human surveillance efforts, must be
developed. Such an observatory would provide a basis for a more educated approach to
assessing the pandemic potential of currently circulating viruses. Furthermore, it would enable
the identification of potential pandemic precursors as they exist in nature. Identifying the
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pandemic potential of viruses can be achieved by analyzing the wealth of existing genetic and
epidemiologic information to determine which risk factors are likely responsible for the
transmission and severity of disease in humans.
x
International organizations such as FAO, OIE, and WHO should fortify their surveillance efforts
through existing mechanisms, particularly in neglected geographical areas and animal
species.
x
International donors and funding agencies involved in influenza research and surveillance
efforts should ensure that data generated through their funding is made readily available to the
scientific community in an equitable, ethical, and efficient manner, as recommended by
Walport and Brest (2011).
x
Full genome sequencing of influenza viruses should be performed on isolates collected
through routine and targeted surveillance, and these sequences should be compulsorily made
available in the public domain in a timely manner.
x
Entities that hold genetic and epidemiological databases for influenza viruses should ensure
compatibility with other datasets and invest in software that can screen sequences for relevant
mutations.
x
An international One Flu effort should be pursued by relevant public health organizations. This
effort should include the use of a flexible risk assessment framework, capable of identifying
and grading the pandemic risk posed by selected animal influenza viruses.
References
World Health Organization. (2011, April 17). Landmark agreement improves global preparedness for
influenza pandemics. [News release]. Retrieved September 9, 2011, from
http://www.who.int/mediacentre/news/releases/2011/pandemic_influenza_prep_20110417/en/index.ht
ml
Walport, M. & Brest, P. (2011). Sharing research data to improve public health. The Lancet,
377(9765), 537–39.
Istituto Zooprofilattico Sperimentale delle Venezie in collaboration with CDC’s Influenza
Division/NCIRD and the One Health Office. (2011). Executive summary of the One Flu Strategic
Retreat, February 1–3, 2011, Treviso, Italy. Retrieved August 9, 2011, from
http://www.cdc.gov/onehealth/pdf/castelbrando/executive-summary.pdf
** A policy position paper prepared for presentation at the conference on Emerging and Persistent
Infectious Diseases (EPID): Focus on Mitigation, convened by the Institute on Science for
Global Policy (ISGP) October 23–26, 2011, at the University of Edinburgh, Edinburgh, Scotland.
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